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Enzymatic reaction mechanisms
119
Enzymatic Reaction Mechanisms b y C Walsh. p p 978. W H F r e e m a n & Co, O x f o r d . 1979. £18.30 The early pioneers of biochemistry were either chemists by training or else biologists and medical men who had to become competent chemists in order to make any headway in the new subject. The biochemicals that now come so conveniently in little brown bottles from St Louis or Mannheim all had first to be isolated and identified by chemical methods. On the other hand, although it gradually became clear that the complex flow of metabolic reactions linking these compounds was governed by macromolecular regulators of great potency and subtlety, the structure of these biological catalysts lay for a long time beyond the reach of chemical methodology. In the past forty years, a remarkable transformation has taken place: gentle purification procedures followed up by amino acid sequencing, X-ray crystallography and latterly NMR have allowed us to build up a minutely detailed picture of the structure of many enzymes. Paradoxically, however, over the same period the sheer expansion of biochemistry has left its students less and less time to build a firm grounding in chemistry. So it comes about that we stand poised to ask questions that our predecessors might never have believed possible, and yet many of us are painfully ill-equipped to answer them. It is as if we had burst into a vast library only to realize that we had forgotten how to read. In Britain this tendency is reinforced in university after university by unhealthily sharp divisions between academic departments of chemistry and of biochemistry. The American scientific establishment has maintained a much more vigorous two-way flow of information between the two disciplines. Not surprisingly, therefore, most of the books which have sought to interpret biochemistry in terms of modern mechanistic organic chemistry have emanated from the United States - - those of Kosower, Ingraham, Bruice and Benkovic, Bender, and Jencks, for example. The latest addition to this distinguished series is Walsh's Enzymatic Reaction Mechanisms, a book, which, as its author acknowledges, clearly owes much to the influence and ideas of R H Abeles and W P Jencks at Brandeis. Biochemistry students, however, will find the information in Walsh's book easier to assimilate into their body of knowledge than that contained in Jencks' earlier classic, Catalysis in Chemistry and Enzymology. Jencks used selected enzymes to illustrate general principles. Walsh, on the other hand, attempts to cover all the major classes of enzymatic reaction. This makes inevitably for a long book (over 900 pages), and the twenty-seven chapter titles in the contents look depressingly like catalogue headings. The completeness of coverage, however, will be welcome to both students and teachers of biochemistry spared the task of risky extrapolation. A book of this size will certainly be used for reference much more often than it will be read from cover to cover. So often in the past i seem to have found that the authors of books on biochemical mechanisms were not interested in the particular topic I wanted to look up. Walsh's thorough coverage should prevent that kind of frustration in the future. The book is understandably strongest where Walsh's own interests lie, with excellent sections on pyridoxal phosphate and flavin catalysis, but everything else seems to be fairly represented too. The author uses a clear positive style throughout, and the book has plenty of crisp line drawings and half-tone illustrations. Chemical formulae are well printed, and the three-dimensional representations are successful despite the lack of colour. A very thorough index, running to over twenty pages, is an excellent feature. Walsh leads the reader in gently with the ingenious device of an introductory section of two chapters which present the book in microcosm. These chapters outline the structure of the rest of the book, introduce the basic concepts and concerns, summarize the major types of enzymatic reaction, present the basic properties of enzymes, and finally discuss the nature of rate enhancement by enzymes and the various possible mechanisms for bringing about the remarkable enhancements that are in fact observed. There follow four further sections - - on group transfers (seven chapters), oxidation and reduction (seven chapters), elimination, isomerization and rearrangement (four chapters), and the making and breaking of C---C bonds (seven chapters). The final chapter, entitled 'The Chemical Logic of Metabolic Pathways' should be especially illuminating for all those undergraduates who see metabolism as a seemingly endless catalogue of gratuitous complexity. For example, why does the metabolism of propionyl CoA proceed via carboxylation at the alpha-carbon to give the branched chain of methylmalonyl CoA, which then has to be rearranged, rather than by direct carboxylation at the beta-carbon to give the desired product, succinyl CoA? This piece of BIOCHEMICAL
EDUCATION
9(3)
1981
apparent metabolic perversity can usually be relied upon to provoke a derisory titter from the more disaffected members of a large biochemistry class. Walsh explains very simply that this route is inevitable since the methyl group of propionyl CoA is not sufficiently activated. Elsewhere he draws attention to the recurrent patterns in metabolism, in fatty acid beta-oxidation as compared with the Krebs cycle, for example. This chapter should be very valuable for teachers and could well be used as compulsory reading for students. As one progresses through the book, there are diversions from time to time to consider in detail some of the relevant experimental approaches to enzyme mechanism. Thus there is a section on isotope effects, another on inhibition studies, another on two-substrate steady-state kinetics, and so on. These potted accounts are well done and should prove useful for students. Inevitably the first edition of a book of this length contains a number of minor errors, eg the NADH absorbance on p 326 which is not only numerically wrong but also apparently independent of path length. The most irritating errors, however, are in the names of enzymes (eg glyoxylase misleadingly for glyoxalase (pp 319-321)), reactions (two out of three wrong in the Meerwein-Ponndorf-Oppenauer reaction (p 318)) and individual research workers (by the score). Students ought to be encouraged to have a proper feeling both for the etymology of biochemical nomenclature and for the importance of bibliographic accuracy, and these errors and inconsistencies certainly do not help. This kind of criticism is really only nit-picking, however. What is undoubtedly far more important is that the scientific content is sound and up to date, and that the book should provide students of biochemistry with a wide range of new insights. This book must be seen as an important contribution to the development of our subject. P C Engel
Department of Biochemistry University of She~ield Sheffield, UK
Immobilized Enzymes: An Introduction and Applications in Biotechnology by M D T r e v a n . pp 138. J o h n Wiley & Sons, Chichester, U K . 1980. £8.75 Immobilized enzymes are of interest to biochemists, microbiologists, chemical engineers and others because of their growing use as industrial catalysts and analytical devices. M D Trevan has squeezed most of the basic principles and practices associated with immobilized enzymes into a slim, concise, easily read volume. The book is well produced with few typographical errors. However, some inconsistencies and omissions occur in the text, for instance, two different but partial definitions of immobilized enzymes are provided in the first few pages. Also, an early general statement of the advantages of using immobilized rather than free enzymes should have been given. Chapter 1 is a short account of methods for immobilizing enzymes. Chapters 2 and 3 deal at some length with the effects immobilization may have on enzyme activity, and the practical applications of immobilized enzymes respectively. A kinetic, biochemical approach is used, dealing at some length with diffusional effects. Chapter 4 speculates on the ways in which immobilized enzyme systems can mimic natural biological systems. Chapter 5 gives full experimental details of a number of immobilization methods. However, no warning is given of the dangers involved in the use of some very toxic reagents such as cyanogen bromide, cyanuric chloride or acrylamide monomer, an omission which should be rectified in future editions. Furthermore, the enzymes and immobilization methods described in this chapter are rather pedestrian and give no impression of how sophisticated methods, designed to immobilize enzymes in a specific form, can be used to solve scientific and technological problems. The author has succeeded in his intention of providing an introductory text for non-experts, rather than a general textbook; to my knowledge, no other publication fills this role. I would recommend this book to the teacher and research worker who wishes to move into this subject, it is probably too specialized for general student purchase, but should prove a useful addition to biochemistry department libraries. P S J Cheetham
Tare and Lyle Ltd Group Research and Development Reading, UK
Enzymatic Reaction Mechanisms b y C Walsh. p p 978. W H F r e e m a n & Co, O x f o r d . 1979. £18.30 The early pioneers of biochemistry were either chemists by training or else biologists and medical men who had to become competent chemists in order to make any headway in the new subject. The biochemicals that now come so conveniently in little brown bottles from St Louis or Mannheim all had first to be isolated and identified by chemical methods. On the other hand, although it gradually became clear that the complex flow of metabolic reactions linking these compounds was governed by macromolecular regulators of great potency and subtlety, the structure of these biological catalysts lay for a long time beyond the reach of chemical methodology. In the past forty years, a remarkable transformation has taken place: gentle purification procedures followed up by amino acid sequencing, X-ray crystallography and latterly NMR have allowed us to build up a minutely detailed picture of the structure of many enzymes. Paradoxically, however, over the same period the sheer expansion of biochemistry has left its students less and less time to build a firm grounding in chemistry. So it comes about that we stand poised to ask questions that our predecessors might never have believed possible, and yet many of us are painfully ill-equipped to answer them. It is as if we had burst into a vast library only to realize that we had forgotten how to read. In Britain this tendency is reinforced in university after university by unhealthily sharp divisions between academic departments of chemistry and of biochemistry. The American scientific establishment has maintained a much more vigorous two-way flow of information between the two disciplines. Not surprisingly, therefore, most of the books which have sought to interpret biochemistry in terms of modern mechanistic organic chemistry have emanated from the United States - - those of Kosower, Ingraham, Bruice and Benkovic, Bender, and Jencks, for example. The latest addition to this distinguished series is Walsh's Enzymatic Reaction Mechanisms, a book, which, as its author acknowledges, clearly owes much to the influence and ideas of R H Abeles and W P Jencks at Brandeis. Biochemistry students, however, will find the information in Walsh's book easier to assimilate into their body of knowledge than that contained in Jencks' earlier classic, Catalysis in Chemistry and Enzymology. Jencks used selected enzymes to illustrate general principles. Walsh, on the other hand, attempts to cover all the major classes of enzymatic reaction. This makes inevitably for a long book (over 900 pages), and the twenty-seven chapter titles in the contents look depressingly like catalogue headings. The completeness of coverage, however, will be welcome to both students and teachers of biochemistry spared the task of risky extrapolation. A book of this size will certainly be used for reference much more often than it will be read from cover to cover. So often in the past i seem to have found that the authors of books on biochemical mechanisms were not interested in the particular topic I wanted to look up. Walsh's thorough coverage should prevent that kind of frustration in the future. The book is understandably strongest where Walsh's own interests lie, with excellent sections on pyridoxal phosphate and flavin catalysis, but everything else seems to be fairly represented too. The author uses a clear positive style throughout, and the book has plenty of crisp line drawings and half-tone illustrations. Chemical formulae are well printed, and the three-dimensional representations are successful despite the lack of colour. A very thorough index, running to over twenty pages, is an excellent feature. Walsh leads the reader in gently with the ingenious device of an introductory section of two chapters which present the book in microcosm. These chapters outline the structure of the rest of the book, introduce the basic concepts and concerns, summarize the major types of enzymatic reaction, present the basic properties of enzymes, and finally discuss the nature of rate enhancement by enzymes and the various possible mechanisms for bringing about the remarkable enhancements that are in fact observed. There follow four further sections - - on group transfers (seven chapters), oxidation and reduction (seven chapters), elimination, isomerization and rearrangement (four chapters), and the making and breaking of C---C bonds (seven chapters). The final chapter, entitled 'The Chemical Logic of Metabolic Pathways' should be especially illuminating for all those undergraduates who see metabolism as a seemingly endless catalogue of gratuitous complexity. For example, why does the metabolism of propionyl CoA proceed via carboxylation at the alpha-carbon to give the branched chain of methylmalonyl CoA, which then has to be rearranged, rather than by direct carboxylation at the beta-carbon to give the desired product, succinyl CoA? This piece of BIOCHEMICAL
EDUCATION
9(3)
1981
apparent metabolic perversity can usually be relied upon to provoke a derisory titter from the more disaffected members of a large biochemistry class. Walsh explains very simply that this route is inevitable since the methyl group of propionyl CoA is not sufficiently activated. Elsewhere he draws attention to the recurrent patterns in metabolism, in fatty acid beta-oxidation as compared with the Krebs cycle, for example. This chapter should be very valuable for teachers and could well be used as compulsory reading for students. As one progresses through the book, there are diversions from time to time to consider in detail some of the relevant experimental approaches to enzyme mechanism. Thus there is a section on isotope effects, another on inhibition studies, another on two-substrate steady-state kinetics, and so on. These potted accounts are well done and should prove useful for students. Inevitably the first edition of a book of this length contains a number of minor errors, eg the NADH absorbance on p 326 which is not only numerically wrong but also apparently independent of path length. The most irritating errors, however, are in the names of enzymes (eg glyoxylase misleadingly for glyoxalase (pp 319-321)), reactions (two out of three wrong in the Meerwein-Ponndorf-Oppenauer reaction (p 318)) and individual research workers (by the score). Students ought to be encouraged to have a proper feeling both for the etymology of biochemical nomenclature and for the importance of bibliographic accuracy, and these errors and inconsistencies certainly do not help. This kind of criticism is really only nit-picking, however. What is undoubtedly far more important is that the scientific content is sound and up to date, and that the book should provide students of biochemistry with a wide range of new insights. This book must be seen as an important contribution to the development of our subject. P C Engel
Department of Biochemistry University of She~ield Sheffield, UK
Immobilized Enzymes: An Introduction and Applications in Biotechnology by M D T r e v a n . pp 138. J o h n Wiley & Sons, Chichester, U K . 1980. £8.75 Immobilized enzymes are of interest to biochemists, microbiologists, chemical engineers and others because of their growing use as industrial catalysts and analytical devices. M D Trevan has squeezed most of the basic principles and practices associated with immobilized enzymes into a slim, concise, easily read volume. The book is well produced with few typographical errors. However, some inconsistencies and omissions occur in the text, for instance, two different but partial definitions of immobilized enzymes are provided in the first few pages. Also, an early general statement of the advantages of using immobilized rather than free enzymes should have been given. Chapter 1 is a short account of methods for immobilizing enzymes. Chapters 2 and 3 deal at some length with the effects immobilization may have on enzyme activity, and the practical applications of immobilized enzymes respectively. A kinetic, biochemical approach is used, dealing at some length with diffusional effects. Chapter 4 speculates on the ways in which immobilized enzyme systems can mimic natural biological systems. Chapter 5 gives full experimental details of a number of immobilization methods. However, no warning is given of the dangers involved in the use of some very toxic reagents such as cyanogen bromide, cyanuric chloride or acrylamide monomer, an omission which should be rectified in future editions. Furthermore, the enzymes and immobilization methods described in this chapter are rather pedestrian and give no impression of how sophisticated methods, designed to immobilize enzymes in a specific form, can be used to solve scientific and technological problems. The author has succeeded in his intention of providing an introductory text for non-experts, rather than a general textbook; to my knowledge, no other publication fills this role. I would recommend this book to the teacher and research worker who wishes to move into this subject, it is probably too specialized for general student purchase, but should prove a useful addition to biochemistry department libraries. P S J Cheetham
Tare and Lyle Ltd Group Research and Development Reading, UK